The polychlorinated dibenzo-p-dioxins are a class of generally toxic compounds which are found as contaminants of preparations of polychlorinated phenols. The most toxic member of this class is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD has an LD50 in the adult male guinea pig of approximately 1 micron g/kg. In spite of the extreme toxicity of these compounds, we do not yet know the biochemical mechanism(s) of their toxicity. Logical mechanisms of toxicity would be inhibition of protein or DNA synthesis, inhibition of mitosis, inhibition of oxidative phosphorylation or interference with the action of hormones like thyroxine. Work in this and other laboratories appear to exclude these as the mechanisms of toxicity of the chlorinated dibenzo-p-dioxins. Another possible mechanism is the excessive and lethal inductin of the activity of enzymes beyond that needed for normal cellular function. One of the enzyme activities which is markedly stimulated by TCDD is DT-diaphorase. The present proposal will attempt to determine if a relationship exists between induction of DT-diaphorase activity by TCDD and the toxicity of TCDD.